Understanding Depression presented by Vanessa Thompson, APRN, GNP-PMHNP-BC Director Inpatient Behavioral Health Services Spartanburg Regional Medical Center

No Conflict of Interest

Clinical Presentation 43 year old female with feelings of helplessness and hopelessness. Stating “I’m not myself; all I want to do is crawl in the bed and sleep so I don’t have to face my problems”. I know I can’t, I need to keep moving. I want my life back, but I don’t see any light at the end of the tunnel. My life seems like it has fallen apart and I can’t seem to get control of it. I have so much to do with little help to do it Life stressors: Husband was in a MVA several months ago (out of work) Mother diagnosed with CA (now moved in with her) Mother of a 13 and 14 year old; both with busy schedules   What would you do for this patient……

What Do We Know About Depression Very common Associated with significant dysfunction Under diagnosed Often chronic or recurrent Commonly present with other general medical conditions Highly treatable Multiple safe and effective treatments are available

Comorbidity Depression and pain often co-occur MDD frequently co-occur with other psychiatric illness (PTSD, Anxiety, Schizophrenia) The 1990-92 National Comorbidity Survey (US) reports that 51% of patients dx with MDD also suffer from a lifetime of anxiety Increase rates of alcohol and drug abuse/misuse and dependence About 1/3 of patients diagnosed with ADHD develop a comorbid depression Depression and pain often co-occur One or more pain symptoms are present in 65% of depressed patients (emotional vs physical pain) 5-85% of patient with pain may suffer from depression 1.5-2 fold increase risk of cardiovascular disease in patient diagnosis with depression

CVD and Depression Patients with cardiovascular disease (CVD) more likely to experience depression1 Patients with depression 1.6 times more likely to develop coronary artery disease (CAD); even more likely with MDD1 Also 4 times more likely to experience a myocardial infarction (MI)1 Post-MI patients with depression less likely to follow lifestyle changes2 Pratt LA et al. Depression, psychotropic medication, and risk of myocardial infarction. Prospective data from the Baltimore ECA follow-up. Circulation. 1996;94(12):3123-3129. Ziegelstein RC et al. Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction. Arch Intern Med. 2000;160(12):1818-1823.

Depression and Obesity 65% of the US population is overweight or obese More obese women than men (54% vs. 46%)1 BMI ≥30 in women associated with nearly 50% increase in lifetime prevalence of depressive disorders2 Ogden CL et al. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006;295(13):1549-1555. Chapman DP et al. The vital link between chronic disease and depressive disorders. Prev Chronic Dis. 2005;2(1):A14.

Depression and Diabetes Depression twice as prevalent in those with diabetes More prevalent in women with diabetes than in men with diabetes Anderson RJ et al. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001;24(6):1069-1078.

Comorbid Medical Conditions Asthma1 Pain2 Arthritis1 Cardiovascular disease1 Stroke3 Diabetes1 Obesity1 Chapman DP et al. The vital link between chronic disease and depressive disorders. Prev Chronic Dis. 2005;2(1):A14. Gureje O et al. A cross-national study of the course of persistent pain in primary care. Pain. 2001;92(1-2):195-200. Gillen R et al. Depressive symptoms and history of depression predict rehabilitation efficiency in stroke patients. Arch Phys Med Rehabil. 2001;82(12):1645-1649.

In the United States about: About 3.4% of people with MDD commit suicide 60% of people who commit suicide had depression or another mood disorder The most common time of onset of MDD is between the ages of 20 and 30 years Later peak between 30 and 40 years Depressed individuals have a shorter life expectancies than those without depression (susceptibility to medical illnesses and suicide)

Drug and Alcohol Use Benzodiazepines are central nervous system depressants increase risk of MDD Toxic effects of sedative-hypnotic drugs including alcohol on neurochemistry decrease the levels of serotonin and norepinephrine or activation of immune mediated inflammatory pathway in the brain. ¼ of patients recovering from alcoholism experience anxiety and depression which can persist for up to 2 years Methamphetamine abuse is also commonly associated with depression

Drug and Alcohol Use Very high level of substance abuse occur in behavioral health patient Especially alcohol, sedatives, and cannabis (where does the patient get them) DSM-5 a diagnosis of mood disorder cannot be made if the cause is believed to be due to “the direct physiological effects of a substance” When a syndrome is resembling MDD is believed to be caused immediately by substance abuse or by and adverse drug reaction it is referred to as “ “Substance-induced mood disturbance” Excessive Alcohol consumption increases the risk of developing MDD

Practice Recommendation Screen patients with any chronic health condition for depression, especially patients with diabetes, cardiovascular disease, or chronic pain. So here is your first practice recommendation. Quite simply: Screen any patients with chronic health conditions for depression, especially those with diabetes, cardiovascular disease, or chronic pain. Source: US Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Intern Med. 2002;136(10):760-764. US Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Intern Med. 2002;136(10):760-764 AAFP Approved source: Institute for Clinical Systems Improvement Website: http://www.icsi.org/depression_5/depression__major__in_adults_in_primary_care_3.html Strength of Evidence: Grade A (randomized, controlled trials)

Two Questions Over the last two weeks: Have you felt down, depressed, or hopeless? (Mood) Have you felt little interest or pleasure in doing things? (Interest)

Two-Steps for Depression Screening Step One: Two-Question Depression Screen Step Two: If Screen is Positive… Over the past 2 weeks have you felt down, depressed, or hopeless? Over the past 2 weeks have you felt little interest or pleasure in doing things? Probe deeper, be proactive, engage in conversation about mood and changes in behavior 24% - 40% of patients with positive screen receive MDD diagnosis Others may have dysthymia, subsyndromal depressive disorders, anxiety, PTSD, substance abuse, panic disorder, or grief disorder A “yes” to either question is a positive initial screen for depression… US Preventive Services Task Force. Screening for depression: recommendations and rationale. Ann Intern Med. 2002;136(10):760-764

Rating scales The score on a rating scale alone is insufficient to diagnosis depression to the satisfaction of DSM or ICD But provides an indication of the severity of symptoms for a time period A person who scores above a given cut off point can be more thoroughly evaluated

Recommended Instruments QIDS: Quick Inventory of Depressive Symptomatology (http://www.ids-qids.org) PHQ-9: Patient Health Questionnaire-9 (www.phqscreeners.com) Both instruments are… Validated Quickly and easily administered and scored Available to download Available in English and Spanish Helpful for initial screening AND evaluation of treatment response

What is Depression…. MDD is mental disorder characterized by a pervasive and persistent: Low mood Low self-esteem Loss of interest of pleasure (in normally enjoyable activities)

What is depression Major Depressive disorder is classified as a mood disorder in DSM-5 The diagnosis can be made on the presence of a single or recurrent major depressive episode. A major depressive episode is characterized by the presence of a severely depressed mood that persists for at least two weeks Episodes may be isolated or recurrent and are categorized as mild (few symptoms minimum criteria) Moderate or severe (mark impact on social or occupation functioning) Episode with psychotic features-commonly referred to as psychotic depression is automatically rated as severe If the patient has had an episode of mania or markedly elevated mood a diagnosis of bipolar disorder is made

MDD is a disabling condition that adversely affects a person’s Family Work School life Sleeping Eating habits

Signs and Symptoms S I G E C A P - Changes in sleep pattern - Changes in interests or activity - Feelings of guilt or increased worry - Changes in energy - Changes in concentration - Changes in appetite - Psychomotor disturbances - Suicidal ideation

Major Depressive Disorder (DSM-5) Core symptoms: SIGECAPS Depressed mood (sad, down, blue) AND/OR Reduced interest or pleasure (I) Somatic symptoms: Change in appetite- significant weight loss (not dieting or weight gain) 5% of body weight in a month)(A) Change in sleep pattern (insomnia or hypersomnia nearly every day)(S) Reduced energy level (E) Psychomotor agitation/retardation (nearly every day) observed by others(P) Cognitive symptoms: Poor concentration/easy distraction (C) Inappropriate guilt/self reproach (G) Thoughts of death, dying, suicide (not just the fear of dying)(S) 5 out of 9 for at least two weeks

Grief MDD Feelings of emptiness and loss Dysphoria in grief likely decrease in intensity over days to weeks occurs like waves Emotions triggered by thoughts or reminders of the deceased Self esteem is generally preserved Persistent depressed mood and inability to anticipate happiness or pleasure Persistent and not tied to specific thoughts or preoccupations Feelings of worthlessness and self- loathing

Signs and Symptoms A depressed person may report multiple physical symptoms such as: Fatigue Insomnia Headache Digestive problems Decrease appetite (resulting in weight loss) Increase appetite (weight gain) stress eating Body aches Severe Cases the patient may have symptoms of psychosis delusions hallucinations (less common) Assess for suicidality… plan, document, and refer

Diagnosis Of MDD Is based on the patient’s self-reported experience Behavior reported by family and friends (if patient gives you permission always follow up with family and friends; a different perspective) Mental status examination

Clinical Assessment Done by a trained LPC, LSIW, LMSW, NP, psychiatrist, or psychologist Record current state Biographical history Current symptoms Family history Social factors Relevant information that may be impacting the patient’s mood Current ways to regulate mood (legal/illegal) Mental State Exam Assess current mood Thought content (helpless or hopelessness) Self harm or suicide and an absence of positive thoughts or plan Rating scales (Hamilton Rating Scale for depression or Beck Depression Inventory)

Differential Diagnoses Dysthymia disorder--(a chronic, milder mood disturbance in which a person reports a low mood almost daily over a 2 year span) Adjustment disorder with depressed mood-- (a mood disturbance appearing as a psychological response to an identifiable event or stressor) Bipolar disorder—also know as manic-depressive disorder is a condition in which depressive phases alternates with mania Substance abuse mood disorders

Diagnosis Of MDD There is no laboratory test to diagnosis a Major Depressive Disorder; however: R/O medical conditions that may mimic MDD TSH and thyroid panel RPR B12 U/A C & S CMP Chest x-ray CBC CT-Scans/MRIs UDS ETHO level Vitamin D HIV Hep C (for those at high risk or have concurrent depression) UCG (r/o pregnancy; medications start) ESR (r/o systemic infection or chronic disease) Testosterone levels (dx hypogonadism as a cause of depression in males) Cortisol level (screen for hypothalamic-pituitary adrenal axis deficiency ) Consider in your lab work-up to add vitamin D level (given risk for MDD, cognitive decline, etc) if deficient as well as possible HIV and HEP C for those who are at risk who have concurrent depression, as sometimes these are risks and causative agents of depression.   Also consider in your lab work to add cortisol to screen for hypothalamic-pituitary-adrenal axis deficiency which could cause concurrent depression.

Explore the Differentials Depressive Disorders Psychiatric Major Psychoses Adjustment D/O w/ depression Bereavement (up to 2 months) General Medical Hypothyroidism = classic rule-out Post-CVA, Post-MI Ca of head of pancreas Substance-Related Alcohol abuse, cocaine/amphetamine withdrawal Rx meds: steroids, b-blockers, a-methyldopa

Common Types of Depression Major Depression Dysthymia Bipolar Disorder Seasonal Affective Disorder (SAD)

Major Depression Dysthymia This type causes symptoms that may: Begin suddenly, possibly triggered by a loss, crisis or change Interfere with normal functioning Continue for months or years It is possible for a person to have only one episode of major depression. It is more common for episodes to be long lasting or to occur several times during a person’s life People with this illness are mildly depressed for years. They function fairly well on a daily basis but their relationships suffer over time.

Season Affective Disorder Bipolar Disorder This is a depression that results from changes in the season. Most cases begin in the fall or winter, or when there is a decrease in sunlight. Bipolar Disorder People with this type of illness change back and forth between periods of depression and periods of mania (an extreme high). Symptoms of mania may include: Less need for sleep Overconfidence Racing thoughts Reckless behavior Increased energy Mood changes are usually gradual, but can be sudden

Subtypes of MDD Melancholic depression-characterized by a loss of pleasure in most or all activities, failure to react to pleasurable stimuli, a depressed mood more pronounce than that of grief or loss, worsening symptoms in the morning hours, early-morning waking, excessive weight loss (not anorexia) Atypical depression-characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite (comfort eating), excessive sleep or sleepiness(hypersomnia), a sensation of heaviness in limbs, significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection Catatonic depression is a rare and sever form of MDD involving disturbances of motor behavior and other symptoms. Here the person is mute and almost stuporous, and either remains immobile or exhibits purposeless or even bizarre movement. Catatonic symptoms also occurs in schizophrenia ore manic episodes, or seen in neuroleptic malignant syndrome.

Subtypes of MDD Postpartum depression associates with puerperium not elsewhere classified, refer to the intense sustained and sometimes disabling depression experience by women after giving birth. Postpartum depression occurs within one month of delivery. It can last up to 3 months post delivery. Has an incidence rate of 10- 15% among new mothers. Seasonal affective disorder (SAD) is a form of depression episodes comes on in the fall or winter and resolves in the spring. The diagnosis is made if at least 2 episodes have occurred in colder months with non at the time over a 2 year period.

Major Depressive disorder also know as: Clinical depression Major depression Unipolar disorder Recurrent depression

Causes of MDD Psychological Psycho-social Hereditary Evolutionary Biological factors Long-term substance abuse/misuse

Causes of Depression Psychological are based on theories of personalities, interpersonal communication and learning Biological theories focus on monoamine chemicals, Serotonin Norepinephrine Dopamine Which are naturally present in the brain and assist communication between nerve cells. Serotonin is hypothesized to regulate other neurotransmitter system; decrease in serotonin activity may allow theses systems to act in unusual and erratic ways. Monoamine hypothesis of depression postulates that a deficiency of certain neurotransmitters is responsible for the corresponding features of depression

Major Neurotransmitters Serotonin Norepinephrine Anxiety Irritability Energy Interest Impulsivity Mood, Emotion, Cognitive function Sex Appetite Aggression Motivation Drive Dopamine

Role of Dopamine in the CNS Dopamine modulates various brain functions Mood Cognition Motor function Drive Aggression Motivation Kaplan HI, Sadock BJ. In: Synopsis of Psychiatry: Behavioral Sciences,Clinical Psychiatry, 8th ed. 1998. Hardman JG, et al. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. 1996.

Role of Serotonin in the CNS Serotonin influences a wide variety of brain functions Mood Sleep Cognition Sensory perception Temperature regulation Nociception (e.g., migraine headache) Appetite Sexual behavior Kaplan HI, Sadock BJ. In: Synopsis of Psychiatry: Behavioral Sciences,Clinical Psychiatry, 8th ed. 1998. Hardman JG, et al. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. 1996. Nemeroff C. Scientific American. June 1998;42-49.

Role of Norepinephrine in the CNS Norepinephrine plays an important role in the brain affecting Mood Learning and memory Regulation of sleep-wake cycle Regulation of hypothalamic-pituitary axis Regulation of sympathetic nervous system Slide 9 Kaplan HI, Sadock BJ. In: Synopsis of Psychiatry: Behavioral Sciences,Clinical Psychiatry, 8th ed. 1998. Nemeroff C. Scientific American. June 1998;42-49.Frazer A. J Clin Psychiatry. 2000;61(suppl 10)25-30.

Causes of Depression Biological Biopsychosocial model propose that biological psychological and social factors all play a role in depression The diathesis-stress model specifies that depression results when a preexisting vulnerability is activated by stressful life event(s) Depression may be directly caused by a damage to the cerebellum Researcher in New Zealand concluded that variation among the serotonin transporter (5-HTT) gene affects the chances a person who experience a very stressful life event will experience depression Swedish study estimated that heritability of depression the degree in which individual difference in occurrence are associated with genetic differences Around 40% of women and 30% of men

Other Hypotheses MRI scans of patients with depression have revealed: A number of difference in the brain structure compared to those who are not depressed Recent meta-analyses of neuroimaging studies in major depression reported that compared to controls depressed patients had increased volume of the lateral ventricles and adrenal gland and smaller volumes of basal ganglia, thalamus, hippocampus and frontal lobe (including the orbitofrontal cortex and gyrus rectus) Hyperintensities have been associates with patients with a late onset, and have led to the development of the theory of vascular depression There may be a link between depression and neurogenesis of the hippocampus a center for both mood and memory. Loss of hippocampal neurons is found in some depressed individuals and correlates with impaired memory and dysthymic mood

Shown here are PET scans of the brain showing different activity levels in a person with depression, compared to a person without depression

this MRI image depicts where a person at high risk for depression has lost a significant portion of brain tissue in the right lateral cortex of ...

Abnormal protein deposits (green) in MDD brain. Depression

Other Hypotheses The hormone estrogen has been implicated in depressive disorder after puberty and reduce rate after menopause Personality and its development appears to be integral to the occurrence of persistence of depression with negative emotions as a common precursor Poverty and social isolation are associated with increased risk of mental illness Child abuse (physical, emotional, sexual, or neglect) is also associated with increased risk of developing depressive disorder later in life.

Treatment Three common treatments for depression Psychotherapy Medication Electroconvulsive Therapy (ECT) Psychotherapy is the treatment of choice (over medications) for people under 18 years Will start with ECT

Psychotherapy This can help many depressed people understand themselves and cope with their problems. For example: Interpersonal therapy works to change relationships that affect depression Cognitive-behavioral therapy helps people change negative thinking and behavior patterns

In-Office Therapeutic Approaches to Management of Depression Supportive Treatment - Identify and reinforce positive behaviors and coping mechanisms that patient has used in the past or is using now “Even though you’ve felt lousy, you have gone to work everyday and done what you need to do. That shows a lot of resilience”. “Let’s think about ways you’ve handled situations like that in the past and see how you can apply those skills you already have”.

Treatment ECT still is the gold standard for treatment resistant major depression with safety and efficacy in the elderly even preferred in pregnancy for psychotic depression due to minimal fetal risks TMS as a relatively newer, non- invasive treatment modality that is FDA-approved for treatment resistant patients or the ones who cannot tolerate medications due to side effects FYI:  the oncology department at SMC recently purchased a device for "brain wave optimization" that is not yet covered by insurance or FDA approved for depression; Hunter Mahon has more information on this should you desire

Treatment Vagal Nerve Stimulation:  also used by neurologist for Parkinson's Disease but requires the surgical implantation of the stimulator (not used widely for depression) Medical Foods (medications such as deplin (L-methylfolate) are used to "supplement" antidepressants  Bright light therapy:  used for seasonal affective disorder (especially in Scandinavian countries who have less sunlight); 10,000 lux of energy 30 minutes a day which uses minimal ultraviolet  light during the fall and winter

TREATMENT The main aims of treatment: improve mood and quality of life reduce the risk of medical complications improve compliance with and outcome of physical treatment facilitate the "appropriate" use of healthcare resources Primary care staff should be familiar with properties and use of: 1) common antidepressant drugs & brief psychological treatments 2) assessment of suicidal thinking and risk Patients with more enduring or severe symptoms will usually require specific treatment - usually drug therapy For patients with suicidal ideation / whose depression has not responded to initial management, specialist referral is the next step

TREATMENT Much depressive illness of all types is successfully treated in primary care Four main reasons for referral to specialist psychiatric services: 1) Condition is severe 2) Failing to respond to treatment (e.g. Psychomotor retardation) 3) Complicated by other factors (e.g. Personality disorder) 4) Presents particular risks (e.g. Agitation and psychotic behaviour) Principal decision is whether to treat with drugs or a talking therapy Most patients in primary care settings would prefer a talking therapy Effectiveness is limited to particular forms of psychotherapy Mild-Mod. Depression: CBT and antidepressants are equally effective Severe Depression: antidepressant drugs are more effective

Algorithm

Treatment for Depression Medication Antidepressants can help ease the symptoms of depression and return a person to normal functioning. Antidepressants are not habit forming.

Treatment Goal The goal of treatment with antidepressant medication in the acute phase is the remission of major depressive disorder symptoms APA Practice Guidelines for the Treatment of Psychiatric Disorders.

Length of Antidepressant Treatment Can take 2-6 week to work (sometimes up to 12 weeks) Always titrate up for best tolerability to side effects Non additive All antidepressants lower the seizure threshold Higher risk with bupropion, amoxapine, and maporotilline Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

Treatment of Depression Most antidepressant medications increase the levels of one or more monoamines-the neurotransmitters serotonin, norepinephrine and dopamine in the synaptic cleft between neurons in the brain.

Antidepressants’ Mechanism of action Once therapy is initiated an increase in neurotransmission occurs The postsynaptic receptors begin to down-regulate This correlates with antidepressant response Down regulation of the postsynaptic receptor takes time after medication is initiated.

Antidepressant Warnings All patients being treated with antidepressants for any indication should be monitored closely for: Clinical worsening Suicidality Unusual changes in behavior Monitor these patients especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Antidepressant Use in Children, Adolescents, and Adults http://www.fda.gov/cder/drug/antidepressants/default.htm

The Suicide Question If an adult, child, or adolescent says, “I want to kill myself, or I'm going to commit suicide” Always take this statement seriously and immediately seek assistance from a qualified mental health professional People often feel uncomfortable talking about death. However, asking the adult, child, or adolescent whether he or she is depressed or thinking about suicide can be helpful. Rather than putting thoughts in the person's head, such a question will provide assurance that somebody cares and will give the person the chance to talk about problems

Suicide Risk Screening Measure Suicide Risk Screening Questions Score Ideation Have you had thoughts of taking your own life 1 Plans Have made any plans to take your life? Means Do you have access to the tools or situation to take your life according to your plan? Intent Do you intend to commit suicide? When? History Have you ever tried to take your own life? Total Depression in Women Series, PACE, 2007

U.S. Suicides 11th leading cause of death 8th leading cause of death for males 19th leading cause of death for females 1.3% deaths suicide 29% heart diseases 23% malignant neoplasms 6.8% cerebrovascular disease

Steps for Choosing an Effective Antidepressant Recognize that some antidepressants may be more effective in certain populations even though most are generally of equal effectiveness. Ask about personal or family history of treatment with antidepressants, particularly about side effects. Consider the burden of side effects, particularly weight gain and sexual side effects in midlife women. Consider drug-drug interactions with other medications the patient is taking or may take. Consider the potential lethality of the antidepressant in the case of an overdose. Use antidepressant side effects for efficacy. Moore DP, Jefferson JW. Mood Disorders. In: Moore & Jefferson: Handbook of Medical Psychiatry, 2nd ed. Philadelphia: Mosby; 2004.

If Initial Treatment Ineffective Medication trial should last 8-12 weeks If no side effects or tolerability issues, increase dosage every 2-3 weeks until Remission achieved Max dose achieved Side effects limit titration Combine antidepressants and psychotherapy Combine antidepressants or consider augmentation trial Considering tailoring your treatment for specific sub-populations (e.g., elderly, midlife women etc). Texas Medication Algorithm Project (TMAP) Treatment of Major Depressive Disorder Clinician’s Manual- http://www.dshs.state.tx.us/mhprograms/tmapover.shtm Kaiser Permanente Care Management Institute. Depression clinical practice guidelines. http://www.guideline.gov/summary/summary.aspx?doc_id=9632&nbr=5152&ss=6&xl=999.

Follow Up after Initial Treatment Individualize visit frequency for each patient Patient’s starting or switching to a new RX should be seen every two weeks until stable Patient’s at increased risk for suicidality or self-injury seen more frequently Contact all patients in early phase of treatment to assess for suicidality or self-injury Assess response with validated tool Texas Medication Algorithm Project (TMAP) Treatment of Major Depressive Disorder Clinician’s Manual- http://www.dshs.state.tx.us/mhprograms/tmapover.shtm

Practice Recommendation Base a choice of antidepressant on the patient’s prior response, patient and clinician preference, potential side effects, and cost. Choose any class of antidepressant as a first-line treatment for MDD. Ask patients from different ethnic groups about their treatment preference for MDD. Choosing an antidepressant is more of an art than an exact science. So there is no specific recommendation on the first antidepressant to choose. AAFP Approved source: National Guideline Clearinghouse. http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=9632&nbr=5152

Practice Recommendation Follow up with patients on antidepressants for MDD: At least once within the first month At least once more 4 to 8 weeks after the first contact Assess for adherence, side effects, suicidal ideation, and response. AAFP Approved Source: National Guideline Clearinghouse. http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=9632&nbr=5152 Strength of evidence: Consensus-based. A practice is recommended based on the consensus or expert opinion of the Guideline Development Team.

Continuation Continuation bridges remission to recovery Patients who remit should continue Rx at least 6-9 months after remission at same dosage at which response was achieved Visits every 3 months Texas Medication Algorithm Project (TMAP) Treatment of Major Depressive Disorder Clinician’s Manual- http://www.dshs.state.tx.us/mhprograms/tmapover.shtml

Major depression and antidepressants Recurrence Rates of Major Depression After 1 year After 2 years After 5 years After 1st espisode 25% 42% 60% After 2nd episode 41% 59% 74% Length of Antidepressant Treatment 1st time depressed 6 month to 1 year 2nd time depressed 2 years (have a 70% chance of relapse) 3 or more times depressed Lifetime therapy with a > 90% chance of relapse Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

Follow-Up Considerations In The First Three Months Week Treatment Actions 2 Check patient compliance to medication usage. Assess for adherence, side effects, suicidal ideation, and patient response. Adjust, as appropriate, medication and dosage. 4 Re-check patient compliance to medication usage. Assess for adherence, side effects, suicidal ideation, and patient response. 6 Adjust, as appropriate, medication and dosage. 7 - 12 Monthly communication with patient; Patients Appointments every 3rd or 4th week; Further Medication or Medication Dosage Adjustments; Goal: Remission

Drug Treatment Tricyclic Antidepressants (TCAs) since the 1950s effective and cheap limit compliance variable degrees of sedation fatal in overdose (except Lofepramine) dose-related anticholinergic side effects, postural hypotension Monoamine Oxidise Inhibitors (MAOI’s) rare fatalities tyramine-free diet Selective Serotonin Re-uptake Inhibitors (SSRI’s) fluoxetine lack sedation - no anticholinergic effects improved compliance less immediate benefit for disturbed sleep safe in overdose single or narrow range of doses works

Drug Treatment Selective Serotonin Re-uptake Inhibitors (SSRI’s) - Newer Sertraline lack sedation - no anticholinergic effects improved compliance favourable on glucose metabolism Platelet SSRI Decreased and favourable of CHD patients Remission Prolonged remission with Sertraline safe in overdose single or narrow range of doses works Dual Norepinephrine and Serotonin Re-uptake Inhibitors (SSRI’s) – Newer Similar in action and benefits as SSRIs but also inhibit the noradrenaline pathways Problem in hypertensive patients

Selective Serotonin Inhibitors (SSRI’s)   Fluvoxamine (Luvox/Luvox CR) Metabolized by P450-12A 80% protein bound Give with food to decrease nausea Usually given in the PM (AM if insomnia occurs) Can give bid Drug interactions MAOis, propranolol, metoprolol Bradycardia/hypotension, Increase digoxin and warfarin levels Citalopram (Celexa) Metobalized by P450-3A4 and P450-2C19 Drug interaction with QT-prolonging drugs (contraindicated) Adult dosing (10-40mg/d (clinical trials showed 60 mg no more effective than 40 mg) 60 mg dose increase QT by about 18.5 msec www.fda.gov/Drugs/DrugSafety/com269086.htm Escitalopram (Lexapro) S-optical isomer (enantiomer) of citalopram 2-4 times as potent as citalopram Little or no drug interactions Dosing 5-20 mg/d (max dose in geriatric patients is 10 mg/day) Fluoxetine (Prozac, Sarafem) VERY LONG T1/2 (4-16 days) May be good for non-compliant patients 95% protein bound Potent inhibitor of P450-2D6 Dosing 10-80 mg/d usually given in AM (to reduce insomnia) Sertraline (Zoloft) >95% protein bound Minor inhibitor of P450-2D6 (not very significant) Dosing 25-200/d usually given in AM (to reduce insomnia) Slightly more GI upset than Prozac Paroxetine (Paxil/Paxil CR/Pexeva) P450-2D6 enzyme inhibitor >Prozac Dosing 10-60 mg/d usually given at HS Most sedating Anticholinergic most likely to cause weight gain of all SSRIs Pregnancy Category D/not good for breast milk FDA as issued a warning in children due to increase emotional lability Busy Slide Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

Other Antidepressants Bupropion (Zyban/Wellbutrin, SR XL/Aplenzin, HBr Salt/Forfivo, XL/Budeprion A derivative of the weight loss medication diethytpropion (Tenuate) Usually dosed in the AM and mid-afternoon (not to late due to insomnia) Not to exceed 450mg/d (150mg TID regular release) or XL and 400 mg/d SR due to seizure risk Contraindicated in those with seizures or eating disorder, or abruptly discontinuing ETOH or BZDs May be as effective as Ritalin for ADD/ADHD in adults Lesser risk of inducing mania in bipolar patient compared to SSRIs Good choice for depressed smokers Duloxetine (Cymbalta) Approved for chronic musculoskeletal pain, GAD, Fibromyalgia and diabetic nerve pain A serotonin and norephinephrine reuptake inhibitor 90% plasma protein binding Elimination ½ life of 12 hours Dosing start with 20 mg qd max dose 120 mg qd or divided bid Contraindicated in Narrow-angle glaucoma SE decrease appetite, sweating, sexual dysfunction, nausea and drowsiness Venlafaxine (Effexor) Approved for GAD, Panic disorder (with/without agoraphobia) and phobia 27% protein binding Cautions with hypertensive patients Dosing 75-375 mg/d Desyenlafaxine (Pristiq) Major metabolite of venlafaxine in and extended release table Dosing 50 mg qd max 100 mg qd ½ life 11 hours Trazodone (Desyrel) Less potent SSRI Dosing 25-400 mg given at HS (used for sleep) or divided Up to 600 mg/d can be used in hospitalized patient 92% protein binding Adverse reaction priapism (very rare) drowsiness, orthostasis, anticholinergic effect Vilazodone (Vilbryd) SSRI + 5HT1 a receptor partial agonist (like buspirone) Available in 10mg, 20mg and 40mg tablets Dosing 10mg/d x 7 days, then 20 mg/d x 7 days, the 40 mg/d thereafter (Give with FOOD) SE diarrhea, nausea, vomiting, insomnia and sexual dysfunction ½ life 25 hours 96-99% protein bound Pregnancy category C Mirtazapine (Remeron) 85% protein binding Dosing 15-45 mg/d usually given at HS SE-somnolence, increase appetite, weight gain, dizziness Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

Antidepressant discontinuation Syndrome (ADS) Antidepressant withdrawal associated with an antidepressant’s side effects Occurs mostly with a short ½ life antidepressant Tricyclics withdrawal may include cholinergic “rebound” Abdominal cramping Diarrhea Parkinsonism Other movement problems Insomnia Nausea, sensory disturbance, anxiety, agitation and flu-like symptoms. Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

Common Antidepressant Side Effects Tricyclic Antidepressants Anticholinergic Side Effects Blurred vision Tachycardia Delirium Constipation Urinary Retention Dry Mouth Decrease Memory Cholinergic rebound upon abrupt d/c CNS Effects Drowsiness (very common) Stimulation (more with 2*amines) Toxic Psychosis (anticholinergic effect) Autonomic Side Effect Nasal Congestion Parkinsonism, Other movement problems Sexual dysfunction (less than with SSRIs) Seizures Highest with Amoxapine and Maprotilline All antidepressant lower seizure threshold Cardiac Side Effects Heart Block-1st or 2nd is contraindicated Arrhythmias-prolong Q-T interval Hypotension/orthostasis Tachycardia (Direct, anticholinergic, and reflex) Other Weight gain Agranulocytosis (rare) Allergic Reactions: Rash, urticarial, photo sensitivity, and fever Hepatic obstruction jaundice (very rare) Endocrinologic (SIADH) Caution in pregnancy and breastfeeding Monoamine Oxidase Inhibitors: Postural hypotension stimulation (most with tranylcypromine) Hepatic complications hydrazine >non hydrazine Arrhythmias-prolong Q-T interval Sexual dysfunction Anticholinergic (less than TCAs) Sedation (most with pheneizine) hypertensive crisis-tyamine-containing foods Selective Serotonin Reuptake Inhibitors: (SSRIs) Sexual dysfunction weight loss weight gain (long term) Hyponatremia anxiety sweating Nausea rare abnormal bleeding insomnia Headache diarrhea Serotonin Norephinephrine Reuptake Inhibitors (SRNIs) Similar to SSRIs Dry mouth hypertension Somnolence (drowsiness) Dizziness orthostatic hypotension Mirtazapine (Remeron) Somnolence Increase appetite with weight gain dizziness Bupropion (Wellbutrin) Anxiety Seizure hypertension Weight loss Insomnia Condensed Psychopharmacology, 2013, A Pocket Reference fro Psychiatry and Psychotropic Medications, Leonard Rappa, PharmD, BCPP and James Wiola, PharmD, BCPP

Other Interventions Obtain an adequate amount of sleep Seek emotional support from family and friends Focus on positive aspects of your life Pace yourself, modify your schedule, and set realistic goals Reduce or eliminate the use of alcohol or drugs Exercise or engage in some form of physical activity Eat a proper, well-balanced diet Don’t make long-term commitments or important decisions unless necessary Don’t assume things are hopeless Don’t engage in “emotional reasoning” (i.e.: because I feel awful, my life is terrible) Don’t assume responsibility for events which are outside of your control Don’t avoid treatment as a way of coping

Clinical Presentation 43 year old female with feelings of helplessness and hopelessness. Stating “I’m not myself; all I want to do is crawl in the bed and sleep so I don’t have to face my problems”. I know I can’t, I need to keep moving. I want my life back, but I don’t see any light at the end of the tunnel. My life seems like it has fallen apart and I can’t seem to get control of it. I have so much to do with little help to do it Life stressors: Husband was in a MVA several months ago (out of work) Mother diagnosed with CA (now moved in with her) Mother of a 13 and 14 year old; both with busy schedules   What would you do for this patient……

Thank You A Special Thanks to Dr. Gravely and Dr Thank You A Special Thanks to Dr. Gravely and Dr. Memon my supervising Physicians